Cellular ‘Cheaters’ Give Rise to Cancer

Maybe it was in “some warm little pond,” Charles Darwin speculated in 1871, that life on Earth began. A few simple chemicals sloshed together and formed complex molecules. These, over great stretches of time, joined in various combinations, eventually giving rise to the first living cell: a self-sustaining bag of chemistry capable of dividing and spawning copies of itself.

While scientists still debate the specifics, most subscribe to some version of what Darwin suggested — genesis as a fortuitous chemical happenstance. But the story of how living protoplasm emerged from lifeless matter may also help explain something darker: the origin of cancer.

As the primordial cells mutated and evolved, ruthlessly competing for nutrients, some stumbled upon a different course. They cooperated instead, sharing resources and responsibilities and so giving rise to multicellular creatures — plants, animals and eventually us.

Each of these collectives is held together by a delicate web of biological compromises. By surrendering some of its autonomy, each cell prospers with the whole.

But inevitably, there are cheaters: A cell breaks loose from the interlocking constraints and begins selfishly multiplying and expanding its territory, reverting to the free-for-all of Darwin’s pond. And so cancer begins.

Although we are getting better at preventing or controlling these rebellions, cancer is an inescapable consequence of multicellularity. A fascinating review, published last month in Philosophical Transactions B, shows how cancer and similar kinds of cellular cheating arise not only in mammals, birds, reptiles, fish, insects and other animals, but also in plants, fungi — in most, if not all, multicellular organisms.

In “Cancer Across the Tree of Life: Cooperation and Cheating in Multicellularity,” researchers at the Institute for Advanced Study in Berlin show how maverick cells in species after species engage in the kind of pathological behavior that can bring down any society.

In a healthy organism, a cell replicates only as frequently as needed to maintain the population and allow for modest growth. Cancer cells begin reproducing wildly, consuming more than their share of resources and spewing poisons that degrade the environment and reshape it to their own advantage.

Through a process called differentiation, normal cells specialize, becoming skin cells, nerve cells, bone cells and so forth. There is a division of labor. But cancer cells “dedifferentiate,” abandoning their assigned roles and pursuing a course beneficial only to themselves.

Under normal circumstances, a cell that goes berserk is quickly eliminated through a mechanism called programmed cell death, or cellular suicide. Cancer cells defeat this safeguard. They refuse to die.

No wonder cancer has become a metaphor for human excess — overpopulation and consumption, environmental pollution, the concentration of resources among a hyperacquisitive 1 percent.

The paper in Philosophical Transactions describes cancerlike phenomena in almost every niche of the biosphere. There is even a kind of growth, calicoblastic epithelioma, occurring among colonies of corals.

A photograph included in the paper shows a tumorous protrusion on the mushroom Agaricus bisporus. In another image, the top of a saguaro cactus erupts in elaborate curlicues of uncontrolled growth called fasciations — pathological but so visually arresting that “crested cacti” are valued by collectors.

The writhing distortions reminded me of those I’ve induced in weeds I sprayed with an herbicide called triclopyr. According to the manufacturer’s literature, the chemical is believed to work by mimicking growth hormones called auxins, causing plant cells to crazily multiply. It’s like chemotherapy in reverse, inducing something akin to cancer.

Not all biologists would agree that every instance described in the paper should be classified as cancerlike. What is clear from the abundance of examples is that multicellular life is a continual struggle between competition and cooperation. Tip the balance too far, and the result might be a malignancy.

In the long run of evolution, the trade-offs between cellular freedom and communalism have frequently paid off. Multicellularity, imperfect as it must be, can be so advantageous that it has evolved independently a number of times during the history of the biosphere.

Most of Earth’s biomass still consists of individual actors — bacteria and other single-celled creatures. Often, however, these microbes also cede some of their independence, banding into primitive collectives, like the invisible biofilms that coat surfaces of hospital equipment or thrive in our mouths as dental plaques. These mutual support societies can be all but invincible to antibiotics.

Yet here too, some research suggests, cooperation can give rise to cheating. Taking advantage of the sustenance and shelter provided by the biofilm, some bacteria will squander resources and thrive at the expense of the others — a microscopic tragedy of the commons.

Even cancer cells, once they gain the upper hand, may also begin cooperating with one another — to the benefit of the tumor and to the peril of its host.

As the cancerous cells divide and mutate, they diverge into separate lineages, or “subclones,” each with different abilities. In a deadly symbiosis, one family of cells might manufacture a substance that benefits the others, which in turn makes other chemicals the tumor needs to grow and colonize remote parts of the body.

Through a complex chemical dance, cancer cells can even beguile healthy cells into doing their bidding, acting in ways that promote the malignancy. It’s a strategy all too familiar in life: cooperate just enough to gain your competitors’ trust and then betray them for your own advantage.

In the end, there are no winners. The cancer destroys its own ecosystem and dies with its host.